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Although metastatic breast cancer (MBC) is treatable, it is not curable and most patients remain on treatment indefinitely. While oncologists commonly prescribe the recommended starting dose (RSD) from the FDA-approved label, patient tolerance may differ from that seen in clinical trials. We report on a survey of medical oncologists' perspectives about treatment-related toxicity and willingness to discuss flexible dosing with patients.We disseminated a confidential survey via social media/email in Spring 2021. Eligible respondents needed to be US-based medical oncologists with experience treating patients with MBC.Of 131 responses, 119 were eligible. Physicians estimated that 47% of their patients reported distressing treatment-related side effects; of these, 15% visited the Emergency Room/hospital and 37% missed treatment. 74% (n = 87) of doctors reported improvement of patient symptoms after dose reduction. 87% (n = 104) indicated that they had ever, if appropriate, initiated treatment at lower doses. Most (85%, n = 101) respondents did not believe that the RSD is always more effective than a lower dose and 97% (n = 115) were willing to discuss individualized dosing with patients.Treatment-related side effects are prevalent among patients with MBC, resulting in missed treatments and acute care visits. To help patients tolerate treatment, oncologists may decrease initial and/or subsequent doses. The majority of oncologists reject the premise that a higher dose is always superior and are willing to discuss individualized dosing with patients. Given potential improvements regarding quality of life and clinical care, dose modifications should be part of routine shared decision-making between patients and oncologists.

Purpose:Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared with older women. Understanding biological differences between breast tumors in young versus older women may lead to better therapeutic approaches for younger patients.Experimental Design:We identified 100 patients ≤35 years old at nonmetastatic breast cancer diagnosis who participated in the prospective Young Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status and grade. Whole-exome sequencing of tumor and germline samples was performed. Genomic alterations were compared with older women (≥45 years old) in The Cancer Genome Atlas, according to intrinsic subtype.Results:Ninety-three tumors from 92 patients were successfully sequenced. Median age was 32.5 years; 52.7% of tumors were hormone receptor-positive/HER2-negative, 28.0% HER2-positive, and 16.1% triple-negative. Comparison of young to older women (median age 61 years) with luminal A tumors (N = 28 young women) revealed three significant differences: PIK3CA alterations were more common in older patients, whereas GATA3 and ARID1A alterations were more common in young patients. No significant genomic differences were found comparing age groups in other intrinsic subtypes. Twenty-two patients (23.9%) in the Young Women's Study cohort carried a pathogenic germline variant, most commonly (13 patients, 14.1%) in BRCA1/2.Conclusions:Somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) occur at different frequencies in young versus older women with luminal A breast cancer. Additional investigation of these genes and associated pathways could delineate biological susceptibilities and improve treatment options for young patients with breast cancer.See related commentary by Yehia and Eng, p. 2209

Supplementary Table from Somatic and Germline Genomic Alterations in Very Young Women with Breast Cancer

Purpose:Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared with older women. Understanding biological differences between breast tumors in young versus older women may lead to better therapeutic approaches for younger patients.Experimental Design:We identified 100 patients ≤35 years old at nonmetastatic breast cancer diagnosis who participated in the prospective Young Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status and grade. Whole-exome sequencing of tumor and germline samples was performed. Genomic alterations were compared with older women (≥45 years old) in The Cancer Genome Atlas, according to intrinsic subtype.Results:Ninety-three tumors from 92 patients were successfully sequenced. Median age was 32.5 years; 52.7% of tumors were hormone receptor-positive/HER2-negative, 28.0% HER2-positive, and 16.1% triple-negative. Comparison of young to older women (median age 61 years) with luminal A tumors (N = 28 young women) revealed three significant differences: PIK3CA alterations were more common in older patients, whereas GATA3 and ARID1A alterations were more common in young patients. No significant genomic differences were found comparing age groups in other intrinsic subtypes. Twenty-two patients (23.9%) in the Young Women's Study cohort carried a pathogenic germline variant, most commonly (13 patients, 14.1%) in BRCA1/2.Conclusions:Somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) occur at different frequencies in young versus older women with luminal A breast cancer. Additional investigation of these genes and associated pathways could delineate biological susceptibilities and improve treatment options for young patients with breast cancer.See related commentary by Yehia and Eng, p. 2209

Purpose:While FGFR1 amplification has been described in breast cancer, the optimal treatment approach for FGFR1-amplified (FGFR1+) metastatic breast cancer (MBC) remains undefined.Experimental Design: We evaluated clinical response to endocrine and targeted therapies in a cohort of patients with hormone receptor–positive (HR+)/HER2− MBC and validated the functional role of FGFR1-amplification in mediating response/resistance to hormone therapy in vitro.Results:In the clinical cohort (N = 110), we identified that patients with FGFR1+ tumors were more likely to have progesterone receptor (PR)-negative disease (47% vs. 20%; P = 0.005), coexisting TP53 mutations (41% vs. 21%; P = 0.05), and exhibited shorter time to progression with endocrine therapy alone and in combination with CDK4/6 inhibitor, but not with a mTOR inhibitor (everolimus), adjusting for key prognostic variables in multivariate analysis. Furthermore, mTOR-based therapy resulted in a sustained radiological and molecular response in an index case of FGFR1+ HR+/HER2− MBC. In preclinical models, estrogen receptor–positive (ER+)/FGFR1-amplified CAMA1 human breast cancer cells were only partially sensitive to fulvestrant, palbociclib, and alpelisib, but highly sensitive to everolimus. In addition, transduction of an FGFR1 expression vector into ER+ T47D cells induced resistance to fulvestrant that could be overcome by added TORC1 inhibition, but not PI3K or CDK4/6 inhibition.Conclusions:Collectively, these findings suggest that while FGFR1 amplification confers broad resistance to ER, PI3K, and CDK4/6 inhibitors, mTOR inhibitors might have a unique therapeutic role in the treatment of patients with ER+/FGFR1+ MBC.

Supplementary figures

Supplementary Figure from Somatic and Germline Genomic Alterations in Very Young Women with Breast Cancer

Background: Prior, retrospective analysis of nightly fasting among women with breast cancer suggests that fasting less than 13 hours per night may be associated with higher risk of breast cancer recurrence. Small studies suggest that fasting duration can influence inflammation, obesity, sleep, and other potential mediators of breast cancer recurrence risk. Prolonged overnight fasting is a simple, nonpharmacological behavioral intervention strategy that may be doable for most patients. We designed this pilot study to prospectively evaluate the feasibility of prolonged overnight fasting among breast cancer survivors. Methods: We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13 hours overnight for a 12-week period among women with a history of early stage breast cancer (I to III) who had completed initial cancer therapy at least 6 months prior. Baseline and end of study assessments included measurements of body mass index (BMI), quality of life (QOL) (Functional Assessment of Cancer Therapy - General (FACT-G)), mood (Hospital Anxiety and Depression Scale (HADS)), fatigue (Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue), levels of physical activity (Godin Leisure-Time Exercise Questionnaire), and blood biomarkers (expanded lipid profile, hemoglobin A1c, C-reactive protein, interleukin-6, tumor necrosis factor alpha, leptin, adiponectin). Patient-reported outcome (PRO) surveys were also administered at 6 weeks. Feasibility was defined as ≥ 60% of participants documenting fasting in the food diary for 13 hours on at least 70% of nights during the study period. Changes in study measures from baseline were evaluated using Wilcoxon signed-rank tests. Results: Between July 2020 and January 2021, we enrolled 40 women with a history of breast cancer. Participants had a median age of 59.9 (range 34.9-76.3) and median time since diagnosis was 4.5 years (range 0.8-20.7). At baseline, BMI was normal (18.5-24.9) in 40.0%, overweight (25-29.9) in 37.5%, and obese (≥30) in 22.5%. Forty-two and a half percent had Stage I cancer, 42.5% stage II, and 15.0% stage III. Sixty-five percent were on hormonal therapy. Ninety-five percent of participants fasted ≥ 13 hours for at least 70% of study days (95% CI 83%-99%). At 6 weeks, there was a statistically significant improvement in anxiety (p=.0007). No other significant changes were seen in PROs. At 12 weeks, there were statistically significant improvements in BMI (p=.0072), anxiety (p=.0141), depression (p=.0048), and fatigue (p=.0105). There was no association between change in BMI during the study and baseline BMI category, age, or endocrine therapy. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12 weeks. Conclusions: Prolonged overnight fasting is feasible in the breast cancer population and may improve BMI, mood, and fatigue without a detrimental effect on overall QOL. The data from this study support the need for a larger, longer randomized study of prolonged overnight fasting in the breast cancer population to further evaluate the effects on body composition, mood, QOL, metabolic markers, and risk of recurrence. Table 1.Impact of Prolonged Overnight Fasting among Breast Cancer SurvivorsStudy AssessmentMedian at baselineMedian at 12 weeksMedian within-participant changep-valueBody Mass Index (kg/m2)26.4225.80-0.380.0072HADS - Depression1.001.00-1.000.0048HADS - Anxiety4.504.00-0.500.0141FACIT - Fatigue47.5049.821.000.0105FACT-G - Quality of Life95.2096.840.910.4933Physical Activity Level40.5039.000.000.3340Hemoglobin A1c (mg/dL)5.455.400.000.2758High-density lipoprotein (mg/dL)72.0073.00-2.000.4688Low-density lipoprotein (mg/dL)92.0099.001.000.5626Total Cholesterol (mg/dL)193.00192.003.000.6569C-reactive protein (mg/L)1.500.90-0.100.1043Interleukin-6 (pg/mL)2.001.90-0.300.1213Tumor Necrosis Factor α (pg/mL)0.740.74-0.050.2898Adiponectin (ug/mL)12.0012.000.000.0682Leptin (ng/mL)7.158.30-0.100.8418 Citation Format: Elizabeth K. O'Donnell, Yael N. Shapiro, Amy Comander, Steven J. Isakoff, Beverly Moy, Laura Spring, Seth Wander, Irene Kuter, Jennifer Shin, Jerry Younger, Michelle Specht, Chryssanthi Kourniotis, Carol Sullivan, Loren Winters, Nora Horick, Jeffrey Peppercorn. Pilot study to assess prolonged nightly fasting in breast cancer survivors (LONGFAST) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-11.

Background: MBC is generally incurable and most patients will remain on treatment indefinitely. Medical oncologists commonly prescribe the Recommended Starting Dose (RSD) from the FDA-approved label based upon clinical trial results, with lower doses typically administered after patients’ experience treatment-related toxicity. However, patient tolerance for the RSD in the real-world setting differs from that of clinical trial participants. We previously reported results from a survey of patients with MBC that revealed patients’ willingness to discuss individualized dosing with medical oncologists (Loeser, ASCO 2021). We now report results from a corresponding survey of medical oncologists. Methods: Patient advocates and medical oncologists from the Patient-Centered Dosing Initiative disseminated a confidential, 28-question online survey to US medical oncologists via professional organizations, social media, and email lists. The survey’s objectives were to understand oncologists’ perspectives regarding the prevalence and severity of treatment-related toxicity, increase recognition of the impact of dosage-related mitigation strategies on clinical outcomes, and determine oncologists’ willingness to discuss flexible dosing approaches when patients with MBC begin a new systemic treatment or experience side effects. Results: 131 medical oncologists responded to the survey within the allotted period (4/26 -5/24, 2021). 12 were excluded from further analysis because they were not US-based medical oncologists or lacked experience treating patients with MBC. Of the 119 eligible participants, 85% specialized in breast cancer, 66% worked in an academic setting, and 82% had practiced for > 5 years. Overall, physicians estimated that 47% of patients reported a distressing treatment-related side effect, 15% visited the ER/hospital, and 37% required a break from treatment. The most common mitigation strategies (96% each) were prescribing supportive medication, offering suggestions for palliation, and lowering the dose. Dose reduction was effective, with 74% of doctors reporting patient improvement thereafter. 87% (n=104) of physicians indicated that they had started patients at a lower dose for various reasons, and 60% noted that these patients felt better than patients commencing the same therapy on the RSD. The drugs/classes most commonly prescribed at lower initial doses were capecitabine (91%), taxanes (60%), and palbociclib (50%). Notably, the majority (85%, n=101) of oncologists surveyed do not believe that the RSD is always more effective than a lower dose, and 97% (n=115) would be willing to discuss drug dosing options with patients based on their unique personal attributes. Conclusion: Medical oncologists reported that a high percentage of patients experience distressing toxicity, a need for acute care, and dose interruptions with standard delivery of therapy for MBC. Many elect to decrease the starting dose for select drugs, and almost all are open to discussing lower initial and successive doses. We conclude that these patient-centered dosing discussions should be part of routine care and may consequently improve QOL for patients with MBC. Citation Format: Anne L Loeser, Aditya Bardia, Mark E. Burkard, Kevin M Kalinsky, Jeffrey Peppercorn, Hope S. Rugo, Martha Carlson, Janice Cowden, Julia Maues, Sheila McGlown, Maryam Lustberg. Patient-centered dosing: Oncologists’ perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-09.

Background: Patients’ understanding of their breast cancer (BC) diagnosis is important in improving treatment adherence, shared decision-making, and clinical trial matching. However, studies have reported discrepancies between electronic medical record (EMR) and patient reported information. Using data collected from a pilot study of the Outcomes4Me patient empowerment and clinical trial matching App, we analyzed concordance of patient reported disease characteristics compared to EMR data. Methods: Data was analyzed from a single institution pilot study (NCT04262518) evaluating the feasibility of introducing the Outcomes4Me app into routine BC care. Eligibility included BC patients with any subtype or stage of invasive cancer presenting with a new diagnosis or for follow-up on active therapy. We compared patient reported characteristics within a study specific survey and/or the Outcomes4Me app for stage (metastatic or not metastatic), recurrence history, hormone receptor status, HER2, and surgery history with the data recorded in the EMR. All statistics were descriptive. We conducted the same comparison between patient reported clinical characteristics among real world users of the Outcome4Me app and EMR records downloaded by that cohort of patients. Results: Between June 2020 and December 2020, 107 patients were enrolled. Baseline demographics: 90% White, 4% Black, 3% Asian; 37% with a college degree, and 43% with post college education; 66% hormone positive/HER2-, 20% HER2+, and 13% triple negative BC; 31% were stage 4. Concordance between the survey or App questionnaire and the EMR is shown in the Table. Comparing EMR and survey data, 62% of patients matched on both HER2 and HR status, and 94% of patients matched with the EMR on metastatic and recurrence status. When surgery and treatment information was included with these features, only 57% of patients matched across all these characteristics. Similar concordance was observed between the App questionnaire and EMR. Excluding the 21% of patients reporting “unsure” HER2 status improved the concordance to 85%. Overall concordance of recurrent or metastatic status was higher than for receptor status. Despite the discordance between EMR and patient-reported disease information, 97% of patients reported that they somewhat or strongly understood their cancer diagnosis. A similar pattern of concordance between the App questionnaire and EMR was observed among a real-world cohort of 636 patients using the Outcomes4Me App who provided medical record access. Conclusion: Self report of hormone receptor and HER2 status had limited concordance with the EMR, in contrast to a high degree of accuracy for self-report of metastatic disease. The limited accuracy of self-report suggests a need for improved patient education regarding their cancer characteristics and a need for caution when relying on self-report for clinical trials matching and targeted patient education. The use of a digital platform that integrates self-report with medical record access may help address these critical needs impacting patient empowerment and care. Concordance Between App Questionnaire, Study Survey and EMR (% of patients)Disease Characteristic Matching CriteriaApp v. EMR (n=85)Survey v. EMR (n=107)App Real World Cohort (n=636)HER2 Status73%66%79%HR Status80%85%80%Combined Receptor Status67%62%73%Metastatic Status94%(n=79)97%(n=98)94%Surgery History83%(n=47)95%96%(n=310)Recurrent Status98%(n=48)97%(n=98)98%(n=411)Recurrent/Metastatic Status93%(n=42)94%(n=98)98%(n=411)Receptor/Recurrent Metastatic Status and Surgery History74%(n=33)57%(n=93)70%(n=201) Citation Format: Steven J Isakoff, Eva Glieberman, Maya Said, Agnes H. Kwak, Emily A. O’Rourke, Amanda Stroiney, Laura Spring, Beverly Moy, Aditya Bardia, Nora Horick, Jeffrey Peppercorn. Accuracy of Patient Self-Reported Breast Cancer Disease Characteristics Compared to the Medical Record in a Trial of the Outcomes4MeDigital Health App [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-08.

Financial toxicity describes the financial burden and distress that can arise for patients, and their family members, as a result of cancer treatment. It includes direct out-of-pocket costs for treatment and indirect costs such as travel, time, and changes to employment that can increase the burden of cancer. While high costs of cancer care have threatened the sustainability of access to care for decades, it is only in the past 10 years that the term “financial toxicity” has been popularized to recognize that the financial burdens of care can be just as important as the physical toxicities traditionally associated with cancer therapy. The past decade has seen a rapid growth in research identifying the prevalence and impact of financial toxicity. Research is now beginning to focus on innovations in screening and care delivery that can mitigate this risk. There is a need to determine the optimal strategy for clinicians and cancer centers to address costs of care in order to minimize financial toxicity, promote access to high value care, and reduce health disparities. We review the evolution of concerns over costs of cancer care, the impact of financial burdens on patients, methods to screen for financial toxicity, proposed solutions, and priorities for future research to identify and address costs that threaten the health and quality of life for many patients with cancer.

BACKGROUND Audio recordings of oncology clinic discussions can help patients retain and understand information about their disease and treatment decisions. Access to this tool relies on acceptance of recordings by oncologists. This is the first study to evaluate experience and attitudes of oncologists toward patients recording clinic visits. METHODS Medical, radiation, and surgical oncologists from 5 US cancer centers and community affiliates were surveyed to evaluate clinicians' experience, beliefs, and practices regarding patient-initiated recordings. RESULTS Among 360 oncologists (69% response rate), virtually all (93%) have experienced patients seeking to record visits. Although 75% are comfortable with recording, 25% are uncomfortable and 56% report concerns ranging from less thorough discussions to legal liability. Most (85%) always agree when patients ask to record, but 15% never or selectively allow recording. Although 51% believe recording is positive for the patient-physician relationship, a sizable minority report that it can lead to less detailed conversations (28%) or avoidance of difficult topics, including prognosis (33%). Views did not vary based on subspecialty, practice setting, or geographic region, but older age and years in practice were associated with more positive views of recording. The majority of clinicians (72%) desire institutional policies to govern guidelines about recordings. CONCLUSIONS Most oncologists are comfortable with patient requests to record visits, but a sizable minority remain uncomfortable, and access to recording varies solely on physician preference. This difference in care delivery may benefit from institutional policies that promote access while addressing legitimate physician concerns over privacy and appropriate use of recordings.

Most patients report pain while taking adjuvant endocrine therapy (AET) for the treatment of breast cancer. While studies have examined patients' experiences with side effects, none solely capture patients' experiences with AET-related pain, a troubling symptom that reduces quality of life and impairs treatment adherence. This study explored themes of AET-related pain to inform future intervention development.Between November 2017 and November 2018, female patients (n = 30) with early-stage breast cancer enrolled between 3 and 36 months post-initiation of AET. Purposeful sampling was stratified by adherence level, age, distress level and time taking AET. Study staff conducted, transcribed and coded semi-structured interviews via inductive thematic coding to identify pain-related themes and achieved high inter-coded reliability (Kappa = 0.96).Several pain-related themes were observed. Attitudes around pain are generally negative, and management needs are largely unmet. Patients reported preferences for non-pharmacological management strategies and cited AET pain as a reason for medication breaks but not discontinuation. Patients within 19 months of starting AET and low adherers reported more intense and disruptive pain.Patients' experiences varied by patient attributes and revealed modifiable factors that may be targeted through behavioural interventions. AET-related pain is a complex side effect for which psychosocial support may be beneficial.

PURPOSE: Treatment goals for patients with metastatic cancer include prolongation and maintenance of quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy; however, data on oncologists' dose selection strategies and beliefs are lacking. METHODS: We conducted an electronic international survey of medical oncologists who treat patients with breast and/or gastrointestinal cancers. Survey questions addressed experiences with, and attitudes toward, dose reduction at initiation (DRI) of a new systemic therapy for patients with metastatic cancer. RESULTS: Among 3,099 eligible oncologists, 367 responded (response rate 12%). Most (52%) reported using DRI at least 10% of the time to minimize toxicities. Gastrointestinal specialists were more likely to report DRI ≥ 10% of the time (72% v 50% of generalists and 51% of breast specialists, P < .005). Of those who dose reduced ≥ 10% of the time, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Overall, 65% agreed it is acceptable to lower starting doses to reduce side effects even if it compromises efficacy; younger clinicians were more likely to agree ( P < .005). There was strong support (89%) for future trials to determine optimal effective, rather than maximum tolerated, dose. CONCLUSION: Oncology practice varies with regard to discussion and individualized selection of starting doses in the metastatic setting. This study demonstrates a need for consideration of shared decision making regarding initial dose selection and strong support among oncologists for clinical studies to define optimal dosing and best practices for individualizing care.

Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.

Research biopsies included in cancer clinical trials have the goal of advancing scientific understanding of the biological bases of cancer and its treatments, but may offer no prospect of direct benefit to participants and often pose more than minimal risk. The research community is examining the ethics of research biopsies increasingly often, especially when they are mandatory for study participation but do not support primary study objectives and thus are "nonintegral" to the study. Ethical concerns center on the limited scientific justification supporting some biopsies, risks to research participants, and the potential for coercion and therapeutic misconception during the informed consent process. There is also a lack of comprehensive oversight of research biopsies by regulatory agencies and institutions. This paper reviews these ethical concerns, discusses the scope of federal oversight, and suggests that institutional review boards (IRBs) should assume a larger role in ensuring the ethical conduct of research biopsies. It concludes with guidance to IRBs on how to weigh the risks, benefits, and acceptability of such biopsies in different contexts that is based on a framework the American Society of Clinical Oncology developed for the inclusion of research biopsies in oncology clinical trials.

Background: Young age at diagnosis is an independent risk factor for recurrence and death from breast cancer (BC), with the greatest impact of young age demonstrated in hormone receptor positive (HR+) disease. Younger women are less likely to be adherent to endocrine therapy (ET), which may contribute to disparate outcomes. Methods: As part of a prospective cohort that enrolled women with BC diagnosed at age ≤40 between 2006-2016, we identified women with HR+, Stage I-III BC. Serial surveys with items assessing socio-demographic and treatment information including medication use are administered 1-2 times per year. Medical record review was used to ascertain stage and HR status and to confirm recurrent disease (locoregional, distant, or new primary breast cancer). Women who initiated ET but discontinued it Citation Format: Shoshana M Rosenberg, Yue Zheng, Philip Poorvu, Kathryn Ruddy, Rachel Gaither, Rulla Tamimi, Lidia Schapira, Jeffrey Peppercorn, Steven Come, Virginia Borges, Ann Partridge. Endocrine therapy non-persistence and recurrence in young women with early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-08.

BACKGROUND Patients with cancer are at risk for both objective and subjective financial distress. Financial distress during treatment is adversely associated with physical and mental well-being. Little is known about whether patients' subjective financial distress changes during the course of their treatment.method This is a cross-sectional study of insured adults with solid tumors on anti-cancer therapy for ≥1 month, surveyed at a referral center and three rural oncology clinics. The goal was to investigate how financial distress varies depending on where patients are in the course of cancer therapy. Financial distress (FD) was assessed via a validated measure; out-of-pocket (OOP) costs were estimated and medical records were reviewed for disease/treatment data. Logistic regression was used to evaluate the potential association between treatment length and financial distress.RESULTS Among 300 participants (86% response rate), median age was 60 years (range 27-91), 52.3% were male, 78.3% had stage IV cancer or metastatic recurrence, 36.7% were retired, and 56% had private insurance. Median income was $60,000/year and median OOP costs including insurance premiums were $592/month. Median FD score (7.4/10, SD 2.5) corresponded to low FD with 16.3% reporting high/overwhelming distress. Treatment duration was not associated with the odds of experiencing high/overwhelming FD in single-predictor (OR = 1.01, CI [.93, 1.09], P = .86) or multiple predictor regression models (OR = .98, CI [.86, 1.12], P = .79). Treatment duration was not correlated with FD as a continuous variable (P = .92).LIMITATIONS This study is limited by its cross-sectional design and generalizability to patients with early-stage cancer and those being treated outside of a major referral center.CONCLUSION Severity of cancer treatment-related financial distress did not correlate with time on treatment, indicating that patients are at risk for FD throughout the treatment continuum. Screening for and addressing financial distress should occur throughout the course of cancer therapy.

OBJECTIVE We aimed to investigate eligibility for breast-conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. BACKGROUND Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NAC influences surgical decisions in young women. METHODS The Young Women's Breast Cancer Study (YWS), a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response (cCR and pCR), and surgery were also assessed. RESULTS Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (p < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%) and family history (5%). From 2006 to 2016, the rates of NST (p = 0.0012), cCR (p < 0.0001) and bilateral mastectomy (p < 0.0001) increased, but the rate of BCS did not increase (p = 0.34). CONCLUSION While the proportion of young women eligible for BCS increased after NST, many patients choose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

Synchronous bilateral breast cancer is uncommon, and its pattern and incidence among younger women is unknown. Here we report the incidence, phenotypes, and long-term oncologic outcomes of bilateral breast cancer in women enrolled in the Young Women’s Breast Cancer Study (YWS). The YWS is a multi-center, prospective cohort study of women with breast cancer diagnosed at age ≤ 40 years. Those with synchronous bilateral breast cancer formed our study cohort. Tumor phenotypes were categorized as luminal A (hormone receptor (HR)+/HER2−/grade 1/2), luminal B (HR+ /HER2+ or HER2− and grade 3), HER2-enriched (HR−/HER2+), or basal-like (HR−/HER2−). Descriptive statistics were used to evaluate tumor phenotypes of bilateral cancers for concordance. Among 1302 patients enrolled in the YWS, 21 (1.6%) patients had synchronous bilateral disease. The median age of diagnosis was 38 years (range 18–40 years). Seventeen (81.0%) underwent genetic testing with 6 found to have pathogenic germline mutations in BRCA1, BRCA2, or TP53. The majority of patients (76.2%) underwent bilateral mastectomy. On pathology, 2 patients had bilateral in-situ disease, 6 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, 10 (76.9%) had bilateral luminal tumors and, when fully characterized, 6 were of the same luminal subtype. Only 1 patient had bilateral basal-like breast cancer. At median follow-up of 8.2 years, 14 patients are alive with no recurrent disease. Bilateral breast cancer is uncommon among young women diagnosed with breast cancer at age ≤ 40. In our cohort, the majority of invasive tumors were of the luminal phenotype, though some differed by grade or HER2 status. These findings support the need for thorough pathologic workup of bilateral disease when it is found in young women with breast cancer to determine risk and tailor treatment.

Purpose: Adjuvant endocrine therapy (AET) prevents recurrence after early-stage, hormone sensitive breast cancer; however, adherence to AET is suboptimal, and efficacious interventions are severely lacking. Barriers to adherence are well established; however, interventions thus far have failed to produce meaningful changes in adherence and have generally not followed guiding principles of psychosocial intervention development. The purpose of this paper is to describe the iterative development, using the National Institutes of Health Stage Model for Behavioral Intervention Development, of an evidence-based, patient-centered, telehealth intervention to enhance adherence, improve symptom management, and reduce distress for patients taking AET after breast cancer, with a focus on 1) a small open pilot study which informed modifications and refinement of the intervention based on quantitative and qualitative patient feedback about feasibility and acceptability; and 2) the underlying theoretical and empirical rationale for each component of the finalized intervention. Clinical implications and directions for future research are discussed.

The 21-gene Breast Recurrence Score test predicts benefit from adjuvant chemotherapy in estrogen receptor-positive, HER2-negative (ER+/HER2−) breast cancer (BC). We examined whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NCT). We identified patients with stage I–III ER+/HER2− BC treated with NCT from the Young Women’s Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤40 years. The 21-gene assay was performed on tumor specimens removed prior to NCT either as part of clinical care or retrospectively for research. Pathological complete response (pCR) was defined as ypT0/is ypN0. The relationship between Recurrence Score result and pCR was evaluated using logistic regression modeling. 76 women received NCT for ER+/HER2− BC and were eligible for this analysis. Median age at diagnosis was 37 years (range 24–40). Scores ranged between 5 and 77 with 50% >25 and 5% 25 was 21% (8/38) vs. 5% in patients with scores

Phase I trials often represent the first occasion where new cancer strategies are tested in patients. Various developments in cancer biology, methodology, regulation, and medical ethics have altered the ethical landscape of such trials. We provide a narrative review of contemporary ethical challenges in design, conduct, and reporting of phase I cancer trials and outline recommendations for addressing each. We organized our review around four topics, supplementing the first three with scoping reviews: (1) benefit/risk, (2) research biopsies, (3) therapeutic misconception and misestimation, and (4) reporting. The main ethical challenges of conducting phase I trials stem from three issues. First, phase I trials often involve higher research burden and scientific uncertainty compared with other cancer trials. Second, many patients arrive at phase I trials at a transitional point in their illness trajectory where they have exhausted standard survival-extending options. Third, phase I trial results play a major role in informing downstream drug development and regulatory decisions. Together, these issues create distinct pressures for study design, ethical review, informed consent, and reporting. Developments in methodology, regulation, cancer biology, and ethical awareness have helped mitigate some of these challenges, while introducing others. We conclude our review with a series of recommendations regarding trial design, ethical review, consent, and reporting. We also outline several unresolved questions that, if addressed, would strengthen the ethical foundation of phase I cancer trials.

Retrospective analysis of nightly fasting among women with breast cancer suggests that fasting 13 h may be associated with a higher risk of breast cancer recurrence. We sought to evaluate prolonged overnight fasting (POF), an accessible nonpharmacological intervention, in a prospective feasibility study.We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13 h overnight for 12 weeks among women with a history of early-stage breast cancer survivors. Baseline and end of study assessments included measurements of body mass index (BMI), blood biomarkers, quality of life (QOL), mood, fatigue, and physical activity. Patient-reported outcome questionnaires were also administered at 6 weeks. Feasibility was defined as ≥ 60% of participants documenting fasting for 13 h on at least 70% of nights during the study period.Forty women with a history of breast cancer were enrolled with a median age of 60 (range 35-76) and median time since diagnosis of 4.5 years (range 0.8-20.7). At baseline, BMI was ≥ 25 in 37.5%. Ninety-five percent of participants fasted ≥ 13 h for at least 70% of study days (95% CI 83-99%). There was a statistically significant improvement in anxiety (p = 0.0007) at 6 weeks and BMI (p = 0.0072), anxiety (p = 0.0141), depression (p = 0.0048), and fatigue (p = 0.0105) at 12 weeks. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12 weeks.POF is feasible among patients with a history of breast cancer and may potentially improve BMI, mood, and fatigue without detrimental effects on overall QOL.

Background Breast cancer in young women is more likely to have higher risk features and be associated with germline BRCA1/BRCA2 mutations. We present the clinicopathologic features of breast cancers in a prospective cohort of young women, and associations between surrogate molecular subtype and BRCA1/BRCA2 mutation status. Methods Histopathological features, biomarker status, tumour stage and BRCA status were collected. Invasive tumours were categorised as luminal A-like (ER + and/or PR + , HER2-, grade 1/2), luminal B-like (ER + and/or PR + , HER2 + , or ER + and/or PR + , HER2-, and grade 3), HER2-enriched (ER/PR-, HER2 + ) or triple-negative. Results In all, 57.3% (654/1143) of invasive tumours were high grade. In total, 32.9% were luminal A-like, 42.4% luminal B-like, 8.3% HER2-enriched, and 16.4% triple-negative. Among different age groups, there were no differences in molecular phenotype, stage, grade or histopathology. 11% (131) of tumours were from BRCA mutation carriers; 64.1% BRCA1 (63.1% triple-negative), and 35.9% BRCA2 (55.3% luminal B-like). Discussion The opportunity to provide comparisons across young age groups, BRCA mutation status, surrogate molecular phenotype, and the identification of more aggressive hormone receptor-positive phenotypes in this population provides direction for future work to further understand and improve disparate outcomes for young women with luminal B-like cancers, particularly BRCA2-associated cancers, with potential implications for tailored prevention and treatment.

Capecitabine is important in breast cancer treatment but causes diarrhea and hand-foot syndrome (HFS), affecting adherence and quality of life. We sought to identify pharmacogenomic predictors of capecitabine toxicity using a novel monitoring tool. Patients with metastatic breast cancer were prospectively treated with capecitabine (2000 mg/m2/day, 14 days on/7 off). Patients completed in-person toxicity questionnaires (day 1/cycle) and automated phone-in assessments (days 8, 15). Correlation of genotypes with early and overall toxicity was the primary endpoint. Two hundred and fifty-nine patients were enrolled (14 institutions). Diarrhea and HFS occurred in 52% (17% grade 3) and 69% (9% grade 3), respectively. Only 29% of patients completed four cycles without dose reduction/interruption. In 39%, the highest toxicity grade was captured via phone. Three single nucleotide polymorphisms (SNPs) associated with diarrhea—DPYD*5 (odds ratio [OR] 4.9; P = 0.0005), a MTHFR missense SNP (OR 3.3; P = 0.02), and a SNP upstream of MTRR (OR 3.0; P = 0.03). GWAS elucidated a novel HFS SNP (OR 3.0; P = 0.0007) near TNFSF4 (OX40L), a gene implicated in autoimmunity including autoimmune skin diseases never before implicated in HFS. Genotype-gene expression analyses of skin tissues identified rs11158568 (associated with HFS via GWAS) with expression of CHURC1, a transcriptional activator controlling fibroblast growth factor (beta = − 0.74; P = 1.46 × 10–23), representing a previously unidentified mechanism for HFS. This is the first cancer pharmacogenomic study to use phone-in self-reporting, permitting augmented toxicity characterization. Three germline toxicity SNPs were replicated, and several novel SNPs/genes having strong functional relevance were discovered. If further validated, these markers could permit personalized capecitabine dosing.

Insomnia is a common issue among patients with breast cancer with a potentially devastating impact on quality of life. It can be caused or exacerbated by multiple disease and treatment-related factors. Despite the prevalence and impact of insomnia, it is rarely addressed systematically in the oncology clinic. We conducted a comprehensive review of insomnia to guide clinical care of patient’s with breast cancer and insomnia. This manuscript reviews the prevalence, etiology, emerging science and both non-pharmacologic and pharmacologic options for treatment of insomnia among patients with breast cancer. Multiple factors contribute to insomnia among patients with breast cancer including endocrine therapy and hotflashes, pain and discomfort from local therapy, and fear of recurrence. If we do identify insomnia, there are treatment options and strategies available to help patients. In particular, there is now a considerable body of evidence supporting the use of psychosocial interventions and behavioral treatments, such as cognitive behavioral therapy for insomnia (CBT-I), yoga, and mind-body programs. It is also important for oncology providers to be educated regarding available pharmacologic therapies and emerging data for cannabis-based therapy. This manuscript provides an up-to-date and comprehensive review of the prevalence, etiology, and treatment approaches available for insomnia for clinicians treating patients with breast cancer. We also address strategies and goals for cancer care delivery and future research.

Background: Current exercise guidelines for clinical populations recommend an exercise therapy (ET) prescription of fixed intensity (moderate), duration (40–50 minutes per session), and volume (120–160 min/wk). A critical overarching element of exercise programming that has received minimal attention is dose scheduling. We investigated the tolerability and efficacy of 2 exercise training dose regimens on cardiorespiratory fitness and patient-reported outcomes in patients with posttreatment primary breast cancer. Methods: Using a parallel-group randomized trial, we randomly allocated 174 postmenopausal patients (2.8 years after adjuvant therapy) with impaired peak oxygen consumption (VO 2 peak) to 1 of 2 supervised exercise training interventions delivered with a standard linear (LET) (fixed dose intensity per session for 160 min/wk) or nonlinear (NLET) (variable dose intensity per session for ≈120 min/wk) schedule compared with a stretching attention control group for 16 consecutive weeks. Stretching was matched to exercise dosing arms on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO 2 peak (mL O 2 ·kg −1 ·min −1 ) from baseline to after intervention. Secondary end points were patient-reported outcomes, tolerability, and safety. Results: No serious adverse events were observed. Mean attendance was 64%, 75%, and 80% for attention control, LET, and NLET, respectively. In intention-to-treat analysis, VO 2 peak increased 0.6±1.7 mL O 2 ·kg −1 ·min −1 ( P =0.05) and 0.8±1.8 mL O 2 ·kg −1 ·min −1 ( P =0.07) in LET and NLET, respectively, compared with attention control. Change in VO 2 peak ranged from −2.7 to 4.1 mL O 2 ·kg −1 ·min −1 and from −3.6 to 5.1 mL O 2 ·kg −1 ·min −1 in LET and NLET, respectively. Approximately 40% of patients in both exercise dosing regimens were classified as VO 2 peak responders (ie, Δ ≥1.32 mL O 2 ·kg −1 ·min −1 ). NLET improved all patient-reported outcomes compared with attention control. Conclusions: Short-term exercise training, independently of dosing schedule, is associated with modest improvements in cardiorespiratory fitness in patients previously treated for early-stage breast cancer. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01186367.

Background: Fear of cancer recurrence (FCR) is prevalent among breast cancer survivors and more intense in younger women. Given that FCR is a powerful determinant of quality of life and is associated with healthcare utilization, identifying who may be at risk for experiencing elevated FCR without resolution can inform the timing and targeting of interventions. Methods: Participants included women diagnosed (dx’d) at age ≤40 enrolled in the Young Women’s Breast Cancer Study, a multi-site prospective cohort surveyed at baseline and regularly in follow-up. Surveys include the 3-item Lasry Fear of Recurrence Index which measures the degree of concern about recurrence and current health using 4-point Likert response options that provide a score ranging from 3-12; higher scores indicate greater concern. Group-based trajectory modeling was used to classify distinct FCR patterns from baseline (median of 5 months from dx) through 3 years post-dx. Multinomial logistic regression was used to identify the associated patient (socio-demographics and BRCA status), disease (stage, ER/PR/HER2) and treatment (surgery, chemotherapy) characteristics associated with each trajectory. Variables significant at p Results: 965 women with Stages 0-III breast cancer were included in the analysis, with a median age at dx of 37. Participants were predominantly non-Hispanic White (85%), partnered (76%) and had completed college (84%). There was a significant decrease in median FCR scores from baseline to year 3 (9 vs. 8, Wilcoxon signed-rank test P In the fully adjusted multinomial model, younger age at dx and Stage 3 and 2 (vs. 1) disease were associated with higher odds of being in the high/stable trajectory. Having a lumpectomy (vs. mastectomy) was associated with higher odds of being in a high/stable as well as moderate/improving trajectory while White (vs. non-White) women had higher odds of being in a trajectory of improving FCR. Receipt of chemotherapy and financial discomfort were significantly associated with assignment to specific FCR trajectories in univariate analyses, however did not remain significant in the adjusted model. Being partnered, BRCA mutation status, and ER/PR/HER2 status were not significantly associated with any FCR trajectory classification in univariate or multivariate analyses. Conclusion: While FCR improves over time for many young women with breast cancer, a substantial minority (26%) had FCR that was severe and did not improve or worsened over time. Younger women with higher stage disease who are at risk for high levels of unresolved FCR may benefit from intervention including early referral to mental health professionals. Ongoing monitoring of women at risk for developing FCR following active treatment is warranted. Table Mean FCR score for each trajectoryBaselineYear 1Year 2Year 3TrajectoriesLow/Stable (N=103)5.725.605.545.45Moderate/Improving (N=331)7.907.487.287.09Moderate/Worsening (N=34)6.748.329.6410.54High/Improving (N=294)9.889.419.088.67High/Stable (N=203)11.0211.0811.0310.88 Citation Format: Lidia Schapira, Yue Zheng, Shari Gelber, Philip Poorvu, Kathryn J Ruddy, Rulla Tamini, Jeffrey Peppercorn, Steve Come, Virginia Borges, Ann Partridge, Shoshana Rosenberg. Trajectories of fear of cancer recurrence in young breast cancer survivors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-09.

Background: Breast cancer arising in young women is more likely to have higher risk features than in older women and more likely to be associated with germline BRCA1 or BRCA2 mutations. We previously reported a higher distribution of luminal B-like tumors among young women. Here we present the clinical and pathologic features of invasive disease in a large prospective cohort of young women with breast cancer, and associations between surrogate molecular subtype and BRCA 1/2 mutation status. Methods: Among 1,297 young women (aged ≤40 years) with breast cancer enrolled from 2006-2016, tumor histopathological features were examined by central review, and biomarker status was extracted from pathology reports. Based on histologic grade and biomarker expression, invasive tumors were categorized as luminal A-like (LA=ER/PR+ and HER2-, histologic grade 1 or 2), luminal B-like (LB=ER/PR+ and HER2+, or ER/PR+, HER2-, and grade 3), HER2 enriched (E) (ER/PR- and HER2+) or triple negative (TN=ER-, PR- and HER2-). Tumor stage, clinical characteristics, and BRCA status were retrieved by medical record review (and patient survey for BRCA status if not in medical record). Results: The majority of women presented with early stage invasive disease (8% stage 0, 32% stage 1, 40% stage 2, 15% stage 3; 5% stage 4). Among invasive tumors with evaluable molecular phenotype (n=1,136), 57% were high grade and the distribution of subtypes was: 33% LA, 42% LB, 8% HER2E, and 16% TN (Table 1). Among different age groups (≤ 30, 31-35, and 36-40 years), there were no significant differences in molecular phenotype, tumor stage, tumor grade or histopathological features including presence of tumor necrosis, lymphocytic infiltration, and central fibrotic focus. 96% of women were tested for BRCA1 and BRCA2 germline mutations, and 127 (11%) tested positive: 65% were BRCA1+, and 35% were BRCA2+ (table 2). Among BRCA1+ patients, 2% of cancers were LA, 30% LB, 5% HER2E, and 62% TN; among BRCA2+, 29% were LA, 56% LB, 2% HER2E, and 13% TN. These proportions were relatively consistent across age groups. BRCA1+ patients’ tumors were proportionately more TN and BRCA2+ patients’ tumors more likely to be LB/HER2 negative (p Table 1. Subtype by age groupTotal (n=1136)≤30 yrs (n=144)31-35 yrs (n=314)36-40 yrs (n=678)p=0.42Luminal A-like377 (33%)48 (33%)99 (32%)230 (34%)Luminal B-like477 (42%)59 (41%)137 (44%)281 (41%)• ER/PR+, HER2-, grade 3245 (22%)27 (19%)68 (22%)150 (22%)• ER/PR+, HER2+232 (20%)32 (22%)69 (22%)131 (19%)HER2E95 (8%)13 (9%)34 (11%)48 (7%)Triple Negative187 (16%)24 (17%)44 (14%)119 (18%) Table 2. Subtype by BRCA statusTotal(n=1136)BRCA1+(n=82)BRCA2+(n=45)No mutation/not tested(n=1009)p Citation Format: Yaileen D Guzman-Arocho, Shoshana M. Rosenberg, Philip Poorvu, Kathryn J. Ruddy, Greg Kirkner, Craig Snow, Rulla M. Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Elena F. Brachtel, Ellen Warner, Ann H. Partridge, Laura C. Collins. Clinicopathological features and BRCA 1/2 status in a large prospective cohort of young women with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-02.

Exercise is recommended for all patients with cancer, but there has been limited study of exercise habits in patients across the spectrum of illness. This pragmatic survey aimed to identify the unmet supportive care needs, self-reported symptoms, and exercise habits among both cancer survivors and patients living with advanced disease to determine adherence to exercise guidelines and to identify barriers and opportunities to improve exercise. An anonymous cross-sectional self-administered paper survey was distributed to patients with cancer presenting for oncology clinic visits at an academic cancer center. Survey measures included presence of symptoms and health problems in addition to weekly time spent exercising, change in exercise levels since diagnosis, interest in exercise, and self-reported barriers. Participants reporting at least 150 min of exercise per week were characterized as adherent to guidelines. Among 640 survey respondents, 570 (89%) completed questions about exercise. Only 44% of cancer survivors and 34% of patients living with advanced disease met current guidelines. Survivors who met exercise guidelines had a lower prevalence of fatigue and memory impairments, but this finding was not seen among patients with advanced cancer. Over 70% of patients with advanced disease and 47% of survivors reported decreasing exercise post-diagnosis compared to pre-diagnosis. Prominent barriers to exercise among both groups included burden of illness and time constraints but interest in increasing exercise was high. There is an opportunity to improve exercise and related outcomes among a large percentage of both cancer survivors and patients living with advanced disease.

BACKGROUND The emotional health of adolescent and young adult (AYA) cancer survivors is compromised both during and after cancer treatment. Targeted programs designed to support AYAs’ ability to cope with stress in the years following treatment completion are lacking. Mind-body programs may ameliorate the negative psychological and emotional effects of stress and assist AYAs with managing the psychosocial challenges of early survivorship. OBJECTIVE Our randomized waitlist-control trial aims to assess the feasibility, acceptability, and preliminary efficacy of a virtual group program (Bounce Back) to promote stress management and resiliency among posttreatment AYAs. METHODS Bounce Back is a stress management and resiliency program delivered via videoconference by a trained mental health clinician. Sessions were adapted from an evidence-based mind-body program (Stress Management and Resiliency Training - Relaxation Response Resiliency Program [SMART-3RP]) grounded in relaxation response elicitation, mindfulness, cognitive behavioral therapy, and positive psychology. Seventy-two AYAs (diagnosed with cancer between ages 14 years and 29 years and had completed cancer treatment within the last 5 years) were randomly assigned to the Bounce Back program or waitlist-control group and completed assessments at baseline, 3 months postbaseline, and 6 months postbaseline. The primary aim of the study is to determine the feasibility and acceptability of the Bounce Back program. Descriptive statistics, including means, frequencies, and ranges supplemented by qualitative exit interview feedback will be used to characterize the sample and to summarize feasibility and acceptability. The exploratory aims are to evaluate the preliminary effects of the program on stress coping and psychosocial outcome measures (ie, anxiety, depression) collected across the 3 time points. RESULTS This study was funded by the National Cancer Institute in July 2017. Study procedures were approved by the Dana-Farber Harvard Cancer Center Institutional Review Board in October 2018 (Protocol 18-428). The randomized trial was conducted from July 2019 to March 2021. Quantitative data collection is complete, and qualitative exit interview data collection is ongoing. Results are expected to be published in peer-reviewed journals and presented at local, national, or international meetings in the coming years. CONCLUSIONS Few evidence-based programs exist that tackle the key transitional issues faced by AYA cancer survivors. Future analyses will help us determine the feasibility and acceptability of the Bounce Back program and its impact on AYA stress coping and psychological well-being. CLINICALTRIAL ClinicalTrials.gov NCT03768336; https://clinicaltrials.gov/ct2/show/NCT03768336 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/34033